SUSCEPTIBILITY TO IMMUNOLOGICALLY MEDIATED FATIGUE IN C57BL 6 VERSUS BALB/C MICE/

Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosi s factor (TNF)-alpha have been proposed to play a role in the pathogen esis of fatigue. In the present study we compared the susceptibility o f two mouse strains to immunologically induced fatigue. Daily running of two strains of mice, Balb/c and C57BL/6, was assessed after a singl e injection of Corynebacterium parvum antigen (2 mg/mouse), Spontaneou s running activity of each animal was compared to mean running distanc e prior to injection, To evaluate the involvement of cytokines in fati gue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cyto kine mRNA expression was analyzed in the brains of mice at different t ime periods after immunologic challenge. A significant difference in r unning activity between the two mice strains was observed after C. par vum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) red uction in running activity (relative to preinjection levels) and slowe r recovery to baseline than Balb/c mice. Injection of antibodies speci fic to either IL-1 beta or TNF-alpha did not alter immunologically ind uced fatigue, suggesting a lack of involvement of these cytokines prod uced outside of the central nervous system (CNS). However, increased T NF-alpha and IL-1 beta mRNA expression was found in the brains of C57B L/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C . parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue, These findings are consistent with the hypothesis that expression of proinflammatory cytokines withi n the CNS plays a role in the pathogenesis of immunologically mediated fatigue. (C) 1996 Academic Press, Inc.